Influence of cyclosporine on the occurrence of nephrotoxicity after allogeneic hematopoietic stem cell transplantation: a systematic review

Abstract

Cyclosporine, a drug used in immunosuppression protocols for hematopoietic stem cell transplantation that has a narrow therapeutic index, may cause various adverse reactions, including nephrotoxicity. This has a direct clinical impact on the patient. This study aims to summarize available evidence in the scientific literature on the use of cyclosporine in respect to its risk factor for the development of nephrotoxicity in patients submitted to hematopoietic stem cell transplantation. A systematic review was made with the following electronic databases: PubMed, Web of Science, Embase, Scopus, CINAHL, LILACS, SciELO and Cochrane BVS. The keywords used were: “bone marrow transplantation” OR “stem cell transplantation” OR “grafting, bone marrow” AND cyclosporine OR cyclosporin OR “risk factors” AND “acute kidney injury” OR “acute kidney injuries” OR “acute renal failure” OR “acute renal failures” OR “nephrotoxicity”. The level of scientific evidence of the studies was classified according to the Oxford Centre for Evidence Based Medicine. The final sample was composed of 19 studies, most of which (89.5%) had an observational design, evidence level 2B and pointed to an incidence of nephrotoxicity above 30%. The available evidence, considered as good quality and appropriate for the analyzed event, indicates that cyclosporine represents a risk factor for the occurrence of nephrotoxicity, particularly when combined with amphotericin B or aminoglycosides, agents commonly used in hematopoietic stem cell transplantation recipients.

The Development of Acute Kidney Disease Following Allogeneic Hematopoietic Stem Cell Transplantation

“…Previous studies reported that the incidence of AKD during transplantation ranged from 17% and 73%. Even this condition is as high as 90% in some studies (11,12). In our study, AKD developed in 32.5% of patients.…”

“…Saddani et al showed that amphotericin B use is an independent risk factor for AKD in HSCT patients (24). It is well know that cyclosporine and amphotericin B may lead to acute tubular necrosis (11). In this study, amphotericin B was applied in 24.7% of patients and amphotericin B use was higher in patients developing AKD.…”

Mortalidade relacionada ao transplante e fatores associados em pacientes submetidos ao transplante de células tronco hematopoiéticas: estudo de coorte

“…Insuficiência renal ou lesão renal aguda foi definida como o aumento da creatinina ≥ 2 vezes o valor basal (70,73) .…”

“…Possíveis explicações para esta taxa reduzida (73,85,86) incluem aspectos identificados neste estudo tais como: a maioria dos pacientes apresentaram compatibilidade HLA, enxerto oriundo de doadores aparentados, associação de dois imunossupressores (CSP e MTX; CSP e MMF) e regime de condicionamento NMA.…”

“…Deve-se considerar que os pacientes de TCTH autólogo apresentam, em geral, um menor escore de risco pré-TCTH (37) . Além disso, pacientes que recebem enxerto autólogo não necessitam de imunossupressores para profilaxia de DECH, o que pode estar associado a menor ocorrência de complicações e consequentemente menor mortalidade (73) . (37) .…”